title: Heterodimerization between the lutropin and follitropin receptors is associated with an attenuation of hormone-dependent signaling.
abstract: The LH receptor (LHR) and FSH receptor (FSHR) are each G protein-coupled receptors that play critical roles in reproductive endocrinology. Each of these receptors has previously been shown to self-associate into homodimers and oligomers shortly after their biosynthesis. As shown herein using bioluminescence resonance energy transfer to detect protein-protein interactions, our data show that the LHR and FSHR, when coexpressed in the same cells, specifically heterodimerize with each other. Further experiments confirm that at least a portion of the cellular LHR/FSHR heterodimers are present on the cell surface and are functional. We then sought to ascertain what effects, if any, heterodimerization between the LHR and FSHR might have on signaling. It was observed that when the LHR was expressed under conditions promoting the heterodimerization with FSHR, LH or human chorionic gonadotropin (hCG) stimulation of Gs was attenuated. Conversely, when the FSHR was expressed under conditions promoting heterodimerization with the LHR, FSH-stimulated Gs activation was attenuated. These results demonstrate that the coexpression of the LHR and FSHR enables heterodimerizaton between the 2 gonadotropin receptors and results in an attenuation of signaling through each receptor.
authors.affiliation: PhD, Department of Molecular Physiology and Biophysics, 5-470 Bowen Science Building, The University of Iowa, Iowa City, Iowa 52242. deborah-segaloff@uiowa.edu.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Feng
authors.forename: Meilin
authors.initials: M
authors.lastname: Zhang
authors.forename: Rongbin
authors.initials: R
authors.lastname: Guan
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Segaloff
mesh_terms: D060807:Bioluminescence Resonance Energy Transfer Techniques; D002462:Cell Membrane / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D008164:Luminescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D055503:Protein Multimerization; D011962:Receptors, FSH / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011974:Receptors, LH / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013499:Surface Properties
chemical_list: D006063:Chorionic Gonadotropin; D008164:Luminescent Proteins; D011962:Receptors, FSH; D011974:Receptors, LH; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D019205:GTP-Binding Protein alpha Subunits, Gs